The regulation of the quantities and types of organelles that leave the neuronal cell body destined for use in the axon and its terminals is not well understood. We had previously found that transport of transmitter undergoes a precise down regulation when most of one branch of the bifurcate axon of an identified serotonergic neuron was removed. We have now investigated further the nature of the regulatory event and the reason for its initiation by eliminating portions of the axonal tree of this neuron. We find that the down regulation is more likely to be due to the loss of synapses than of axon because transport of [3H]serotonin decreases as much when an axonal branch is transected distally as after a proximal transection. Transport of [3H]fucosyl glycoprotein, which normally is associated with the serotonergic vesicle in this axon, decreases to the same extent as transport of [3H]serotonin following proximal transection. The glycoprotein down regulation occurs much more rapidly, possibly due to an inhibition of vesicle synthesis. A secondary rise in transport of [3H] fucosyl glycoprotein 3 days to 2 weeks after axotomy suggests that the radiolabeled glycoprotein has undergone a redistribution into organelles not normally labeled and transported in intact neurons in large amounts, since [3H]serotonin transport remains stably diminished during this period. We also describe here a case of routing of rapidly transported material. When one axonal branch is cut far from the point of bifurcation (-10 mm), ["Hlserotonin is directed away from the branch lacking its synaptic terminals and into the remaining intact branch even though the transected branch is physically capable of transporting its normal amount of [3H]serotonin. We suggest that the presence of synaptic endings influences both the export of transmitter vesicles from the cell body and the partitioning of vesicles among axon collaterals.Fast axonal transport supplies axon collaterals and terminals with newly synthesized organelles and macromolecules from the cell body of the neuron (Ochs, 1982). The collaterals and terminals are themselves incapable of synthesizing these materials. In a healthy mature